scholarly journals Relapse or Re-Infection, the Situation of Recurrent Tuberculosis in Eastern China

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Shao ◽  
Honghuan Song ◽  
Guoli Li ◽  
Yan Li ◽  
Yishu Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Eastern China ◽  
Drug Susceptibility ◽  
Population Based ◽  
Variable Number ◽  
Efficient Treatment ◽  
Significant Difference ◽  
Mdr Tb ◽  
Culture Positive ◽  
Recurrent Tuberculosis

PurposeRecurrent tuberculosis (TB) is defined by more than one TB episode per patient and is caused by re-infection with a new Mycobacterium tuberculosis (Mtb) strain or relapse with the previous strain. Recurrence of TB is one important obstacle for End TB strategy in the world and elucidating the triggers of recurrence is important for the current TB control strategy in China. This study aimed to analyze the sources of recurrent TB by the molecular genotyping method.MethodA population-based surveillance was undertaking on all culture-positive TB cases in Jiangsu province, China from 2013 to 2019. Phenotypic drug susceptibility test (DST) by proportion method and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) were adopted for drug resistance and genotype detection.ResultsA total of 1451 culture-positive TB patients were collected and 30 (2.06%, 30/1451) TB cases had recurrent TB episodes. Except 7 isolates were failed during subculture, 23 paired isolates were assessed. After genotyping by MIRU-VNTR, 12 (52.17%, 12/23) paired recurrence TB were demonstrated as relapse and 11 (47.83%,11/23) paired cases were identified as re-infection. The average interval time for recurrence was 24.04 (95%CI: 19.37-28.71) months, and there was no significant difference between relapse and re-infection. For the relapsed cases, two paired isolates exhibited drug resistance shifting, while four paired isolates revealed inconsistent drug resistance among the re-infection group including two multidrug-resistant tuberculosis (MDR-TB) at the second episode.ConclusionRelapse and re-infection contributed equally to the current situation of recurrence TB in Jiangsu, China. Besides, more efficient treatment assessment, specific and vigorous interventions are urgently needed for MDR-TB patients, considering obvious performance among re-infection cases.

scholarly journals 801. Emergence of Multi-Drug Resistance Tuberculosis During the Treatment Course of Pan-Susceptible TB: A Case Series

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S287-S287
Author(s):  
Mary Ford ◽  
Kathryn Lago ◽  
Quratulain Kizilbash ◽  
Adriana Vasquez
Keyword(s):  
Drug Resistance ◽  
Case Series ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Multi Drug Resistance ◽  
Directly Observed Therapy ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Different Strains ◽  
Culture Positive

Abstract Background Successful treatment of tuberculosis (TB) requires monitoring for clinical, radiographic, and microbiologic improvement. Even after negative cultures are obtained, there should be continued monitoring of sputa. If cultures become positive during treatment of drug susceptible TB (DS-TB), there should be concern for multi-drug-resistant tuberculosis (MDR-TB). We present two cases diagnosed with DS-TB who developed MDR-TB during treatment. Case Report: Case 1 is a 33-year-old male who was incarcerated in Peru. During incarceration in 2008, three of his cellmates had MDR-TB and he was diagnosed with DS-TB and treated with directly observed therapy (DOT) for 7 months. In Texas in 2015 he was diagnosed with DS-TB and was initiated on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). Five months into DOT, his sputa became culture positive with molecular detection of drug resistance (MDDR) and drug susceptibility testing (DST) revealing resistance to all of RIPE. Repeat MDDR and DST of the 2015 isolate showed no resistance. Genotyping of the two isolates were identical by mycobacterial interspersed repetitive units (MIRU) and spoligotyping. However, whole genome sequencing showed two different isolates. Case 2 is a 63-year-old female diagnosed with DS-TB in Saipan and started on RIPE in April 2017. She was on DOT until July when she moved to Texas and was lost to follow-up until September. She claims adherence with rifampin and isoniazid during this time. All sputa collected between diagnosis and September were smear and culture negative. Six months into therapy, she had sputa that was culture positive with MDDR and DST showing MDR-TB. Her isolates from Saipan and Texas were sent for genotyping. The MIRU and spoligotyping showed two different isolates. Conclusion These cases show the importance of following cultures throughout treatment. Traditionally, MDR-TB is thought to be due to poor adherence. However, in high prevalence areas, heterogeneous infection with two different strains is an important consideration for the cause of MDR-TB. Concomitant infection of DS and MDR-TB can occur with MDR-TB not being detected until far into therapy. These cases represent heterogeneous exogenous infection of DS and MDR-TB—only discovered after meticulous culture monitoring. Disclosures All authors: No reported disclosures.

scholarly journals Anti-tuberculosis drug resistance pattern among pulmonary tuberculosis patients with or without HIV infection in Mwanza, Tanzania

2012 ◽  
Vol 14 (4) ◽  
Author(s):  
Nyagosya Range ◽  
Henrik Friis ◽  
Said Mfaume ◽  
Pascal Magnussen ◽  
John Changalucha ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Susceptibility ◽  
Ratio Method ◽  
Multi Drug Resistance ◽  
Resistance Pattern ◽  
Newly Diagnosed ◽  
Drug Resistance Pattern ◽  
Mdr Tb ◽  
Susceptibility Tests ◽  
Culture Positive

Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control, particularly multi-drug resistance TB (MDR-TB). The objective of this study was to determine the prevalence of primary and acquired anti-TB drug resistance among newly diagnosed pulmonary TB (PTB) and relapse cases. Sputa were collected from newly diagnosed and relapse PTB patients. Drug susceptibility tests (DST) were performed on sputum culture positive isolates of Mycobacterium tuberculosis using resistance ratio method on four first-line anti-TB drugs: rifampicin, isoniazid, ethambutol and streptomycin. Demographic and anthropometric information was collected and HIV status was determined. Of the 523 culture positive isolates, DST results were available for 503 (96%), 455 were new and 48 were relapse cases. Resistance to at least one of the four drugs was observed in 7.8% (39/503) of the isolates, 7.3% (33/455) were new and 12.5% (6/48) were from relapse cases. Mono resistance to isoniazid was higher in both among new 45.5% (15/33) and relapse 50.0% (3/6) cases. Resistance to rifampicin and streptomycin alone was equal 4/33 (12.1%) and only among new cases. Resistance to ethambutol alone was only one among new cases. Overall MDR-TB prevalence was 2.4% (12/503), nine were new and three were relapse cases. MDR-TB was 17.9% (7/39) for rifampicin and isoniazid. Prevalence of HIV was 43.3% and was similar among new and relapse cases and not risk factor for drug resistance. Majority of PTB patients (52%) had BMI below 18 kg/m2. Those with BMI greater than 18 kg/m2 were more likely to develop drug resistance than those with BMI below 18 kg/m2  (P=0.004). With the resurgence of TB and the high prevalence of HIV among TB patients, prevalence of drug resistance is still low both among new and relapses cases. Despite the current low drug resistance, there is a need for continuous monitoring of the resistance.

scholarly journals Drug resistance gene mutations and treatment outcomes in MDR-TB: A prospective study in Eastern China

2021 ◽  
Vol 15 (1) ◽  
pp. e0009068
Author(s):  
Qiao Liu ◽  
Dandan Yang ◽  
Beibei Qiu ◽  
Leonardo Martinez ◽  
Ye Ji ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Outcomes ◽  
Eastern China ◽  
Multivariable Analysis ◽  
Resistance Mutation ◽  
Gene Mutations ◽  
Drug Resistance Mutation ◽  
Drug Susceptibility ◽  
Phenotypic Resistance ◽  
Mdr Tb

Background Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to TB control. It is of great value to search for drug resistance mutation sites and explore the roles that they play in the diagnosis and prognosis of MDR-TB. Methods We consecutively enrolled MDR-TB patients from five cities in Jiangsu Province, China, between January 2013 and December 2014. Drug susceptibility tests of rifampin, isoniazid, ofloxacin, and kanamycin were routinely performed by proportion methods on Lowenstein–Jensen (LJ) medium. Drug resistance-related genes were sequenced, and the consistency of genetic mutations and phenotypic resistance was compared. The association between mutations and treatment outcomes was expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Results Among 87 MDR-TB patients, 71 with treatment outcomes were involved in the analysis. The proportion of successful treatment was 50.7% (36/71). The rpoB gene exhibited the highest mutation rate (93.0%) followed by katG (70.4%), pncA (33.8%), gyrA (29.6%), eis (15.5%), rrs (12.7%), gyrB (9.9%) and rpsA (4.2%). Multivariable analysis demonstrated that patients with pncA gene mutations (adjusted OR: 19.69; 95% CI: 2.43–159.33), advanced age (adjusted OR: 13.53; 95% CI: 1.46–124.95), and nonstandard treatment (adjusted OR: 7.72; 95% CI: 1.35–44.35) had a significantly higher risk of poor treatment outcomes. Conclusions These results suggest that Mycobacterium tuberculosis gene mutations may be related to phenotypic drug susceptibility. The pncA gene mutation along with treatment regimen and age are associated with the treatment outcomes of MDR-TB.

scholarly journals Mycobaterial interspersed repetitive units-variable number of tandem repeats analysis and pattern of drug resistance in extended drug resistant (XDR) TB isolates from pulmonary tuberculosis patients in Bangladesh

2020 ◽  
Vol 46 (1) ◽  
pp. 22-28
Author(s):  
Shirin Tarafder ◽  
Md Bayzid Bin Monir
Keyword(s):  
Drug Resistance ◽  
Molecular Typing ◽  
Tandem Repeats ◽  
Variable Number ◽  
Drug Resistant ◽  
Gyra Gene ◽  
Drug Resistant Tuberculosis ◽  
Tree Analysis ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Background: To investigate the spread of specific genotypes in a defined geographical area and to determine any relationship of these genotypes with drug resistance the most essential method is molecular typing. It allows a rapid and precise species differentiation. Objective: This study was intended to observe the genotypes of XDR mycobacterium tuberculosis by determining 24 loci MIRU-VNTR analysis. Methods: To gain an insight about molecular typing of MTB and drug resistance-associated mutations in XDR-TB isolates a total of 98 multi drug resistant tuberculosis (MDR-TB) isolates collected through Xpert MTB/RIF assay. They were subjected to 2nd line (Fluoroquinolones, kanamycin, capreomycin and amikacin) drug susceptibility testing through line probe assay (LPA) in a view to detect extensively drug resistant tuberculosis (XDR-TB). Genotyping was done for XDR-TB isolates using 24 loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) using the online tool at http://www.MIRU-VNTRplus.org.. Out of 98 MDR-TB isolates 11(11.23%)  XDR-TB isolates were typed and analysed. Results: Twenty four loci MIRU-VNTR genotyping involving similarity searching and phylogenetic tree analysis revealed that six (54.60%) XDR-TB isolates belonged to Beijing strain, Other MTB strain also detected were Delhi/CAS two(18.20%), Haarlem two(18.20%) and New-1, one (9.10%) in number. Minimum spanning tree analysis showed two strain of Beijing family form a clonal complex. Beijing strains were more common among younger age group and within urban population. Beijing strains were also predominant in treatment failure patient. Only one new case of XDR-TB belongs to Delhi/CAS family. Second line mycobacterial drug resistance (MTBDRsl) detected by LPA showed the most prevalent mutations involved in Fluoroquinolones drug resistance (FQ) was Asp94Gly in gyrA gene (54.55%) in quinolone resistance determining region (QRDR) and for Injectable 2nd line Drug resistance (ISL) was A1401G, C1402T in 16S rrs gene (100%)..  All XDR-TB isolates showed resistance to Levofloxacin in 2nd line LPA but Moxifloxacin showed low level resistance to some cases. Conclusion: Molecular typing of XDR- TB isolates and pattern of drug resistance associated mutations in XDR-TB isolates in Bangladesh have not been reported previously. The result of this study highlights the need to reinforce the TB policy in Bangladesh with regard to control the spread and transmission as well as detection and treatment strategies regarding XDR-TB. Bangladesh Med Res Counc Bull 2020; 46(1): 22-28

scholarly journals Drug-resistant Mycobacterium tuberculosis and its genotypes isolated from an outbreak in western Thailand

2020 ◽  
Author(s):  
Janisara Rudeeaneksin ◽  
Benjawan Phetsuksiri ◽  
Chie Nakajima ◽  
Supranee Bunchoo ◽  
Krairerk Suthum ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Drug Resistant ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Vntr Analysis

Abstract Background Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand. Methods Seventy-two isolates, which included 7% mono-, 30.6% MDR and extensively drug-resistant TB (XDR-TB), were genotyped by spoligotyping, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) and single nucleotide polymorphism genotyping, and their drug resistance was analysed. Results The spoligotyping results showed that Beijing spoligo-international type (SIT)1 was predominant (n=38; 52.8%) while the remaining were non-Beijing sublineages (n=34). The MIRU-VNTR analysis showed that Beijing isolates, most of which belonged to the modern type (n=37), formed 5 clusters and 13 individual patterns. In katG, only mutation Ser315Thr was identified. In rpoB, Ser531Leu was predominant, except for His526Arg and Leu533Pro, which were found in two isolates. A cluster of 14 Beijing strains contained these common mutations and shared the MIRU-VNTR genotype with isolates in the Thamaka district that had spread previously. Two U SIT523 isolates contained the mutations A1400G in rrs and Asp94Gly in gyrA genes, indicating a spread of XDR-TB. Conclusions Most mutations were associated with drug resistance and the specific MDR Beijing and XDR-TB in U SIT523 isolates remain. This genotyping is a key tool for tracking TB transmission in the Thamaka district of Thailand.

scholarly journals Development of Drug Resistance among Comorbid and Non-Comorbid HIV-Negative Relapsed Cases of Tuberculosis in Lahore, Pakistan

2020 ◽  
Author(s):  
Arslan Ahmed Salam ◽  
Aamer Ikram ◽  
Maha Fatima ◽  
Najma Javed Awan
Keyword(s):  
Drug Resistance ◽  
Drug Susceptibility ◽  
Susceptibility Test ◽  
Rifampicin Resistance ◽  
Drug Susceptibility Test ◽  
Health Crisis ◽  
Mdr Tb ◽  
History Of ◽  
Xpert Assay ◽  
Hiv Negative

Abstract Background: Mycobacterium tuberculosis sometimes become resistant to the drugs that are used to treat it. Drug resistant TB (DR-TB) is spread in the same way as drug susceptible TB. DR-TB is a public health crisis. This study aims to find the pattern of drug resistance and correlations between drug resistance and comorbid/non-comorbid conditions in patients with a relapse of TB. Methodology: A cross-sectional study was conducted among 200 HIV-negative relapsed TB patients from 2016-2017 in Mayo Hospital Lahore. The patients’ sputum samples were tested by Ziehl-Neelsen staining to observe acid-fast bacilli. The demographics and medical history of patients was recorded, who were positive for AFB in their sputum samples. Molecular procedure of Gene-Xpert assay was conducted to detect the presence of MTB and rifampicin resistance in the samples. Whereas, the drug susceptibility test (DST) was conducted on the LJ culture medium containing drugs.Results: Out of 200 relapsed TB cases; 97 were comorbid, 99 were non-comorbid. The most prevalent comorbidities were hypertension (42 cases- 43.3%), diabetes (45 cases-46.4%) and hepatitis B (14 cases-14.4%). Among 97 comorbid patients; 37 worked as laborers, 43 earned less than 20,000 PKR and 23 were found to have a history of imprisonment. Whereas in non-comorbid patients; 20 worked as laborers, 28 earned less than 20,000 PKR and 12 had been in prison before. The Gene-Xpert test detected rifampicin resistance (RR) in 20 comorbid (20.6%) and 33 non-comorbid (33.3%) patients. Whereas, the drug susceptibility test (DST) showed that 22 comorbid (22.7%) and 33 non-comorbid (33.3%) patients were RR. A contrast was seen in the results of Gene-Xpert and DST; Gene-Xpert detected 3 cases of RR-negative whereas the same 3 cases were found to be RR-positive on DST. Only 1 case was RR-positive on Gene-Xpert but RR-negative on DST. 17 comorbid patients (17.5%) were diagnosed with MDR-TB and 5 (5.2%) with XDR-TB. Whereas, in non-comorbid patients, there were 26 cases of MDR-TB (26.3%) and 5 cases of XDR-TB (5.1%). There were 2 patients (2.1%) resistant to all drugs.Conclusion: There was a deviation in the results of molecular Gene-Xpert assay compared to the conventional culture methods. Drug resistance was relatively higher in non-comorbid patients than comorbid patients, however, the difference between the two is not very significant.

scholarly journals Resistance at No Cost: The Transmissibility and Potential for Disease Progression of Drug-ResistantM. Tuberculosis

2018 ◽  
Author(s):  
Mercedes C. Becerra ◽  
Chuan-Chin Huang ◽  
Leonid Lecca ◽  
Jaime Bayona ◽  
Carmen Contreras ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Pulmonary Tb ◽  
Genetic Fingerprint ◽  
Resistant Tuberculosis ◽  
Significant Difference ◽  
Mdr Tb ◽  
The Impact

AbstractBackgroundThe future trajectory of drug resistant tuberculosis strongly depends on the fitness costs of drug resistance mutations. Here, we measured the association of phenotypic drug resistance and the risk of TB infection and disease among household contacts (HHCs) of patients with pulmonary TB.MethodsWe evaluated 12767 HHCs of patients with drug sensitive and resistant pulmonary TB at baseline, two, six, and 12 months to ascertain infection status and to determine whether they developed tuberculosis disease. We also assessed the impact of drug resistance phenotype on the likelihood that a TB strain shared a genetic fingerprint with at least one other TB patient in the cohort.FindingsAmong 3339 TB patients for whom were DST available, 1274 (38%) had TB that was resistant to at least one drug and 478 (14⋅3%) had multi-drug resistant (MDR) TB, i.e. TB resistant to both INH and rifampicin. Compared to HHCs of drug sensitive TB patients, those exposed to a patient with MDR-TB had an 8% (95% CI: 4-13%) higher risk of infection by the end of follow up. We found no statistically significant difference in the relative hazard of incident TB disease among HHCs exposed to MDR-TB compared to DS-TB (Adjusted HR 1⋅28 [(95% CI: ⋅9-1⋅83]). Patients with MDR-TB were more likely to be part of a genetic cluster than were DS-TB patients.InterpretationClinical strains of MDR M. tuberculosis are neither less transmissible than drug sensitive strains nor less likely to cause disease. (ClinicalTrials.gov number,NCT00676754)FundingNational Institutes of Health: NIH/NIAID CETR U19AI109755StatementAll authors have seen the manuscript and approved the manuscript.

scholarly journals Inquiry into GeneXpert as a complementary MDR-TB diagnostic tool in North Korea: A follow-up study of North Korean TB drug resistance patterns

2021 ◽  
Author(s):  
Noori Lee ◽  
Hojeong Kwon ◽  
Yoohyun Hwang ◽  
Sungweon Ryoo
Keyword(s):  
Drug Resistance ◽  
Diagnostic Tool ◽  
North Korea ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Diagnostic Tools ◽  
The North ◽  
Resistance Patterns ◽  
Mdr Tb

Abstract Background: This study aims to investigate the usefulness of GeneXpert MTB/RIF (Xpert) in diagnosing rifampicin (RIF) resistance among the patients in the secluded sanatoria of North Korea. This article is a follow up of a report that explored the characteristics of drug resistance in North Korean Sanatoria, published in 2017. Xpert is used as a diagnostic tool to check for multidrug-resistant tuberculosis (MDR-TB) in specific areas of North Korea by the Eugene Bell Foundation (EBF). While there are other diagnostic tools are used to test for RIF resistance, there is no other feasible method to consistently test for MDR-TB in North Korea. Currently, EBF exclusively uses Xpert in tuberculosis and RIF resistance diagnosis when providing medical support for tuberculosis patients in North Korea, where there is limited international access. Methods: We performed Xpert using cultured tuberculous bacilli of North Koreans and compared the result to the corresponding phenotypic drug susceptibility tests (pDST) and rifampicin resistant-determining region sequencing (RRDR). All samples were target-sequenced at the rpoB region, where unique RIF resistance related mutations, potentially specific to North Korea, were discovered.Results: Using the RRDR sequencing as the gold standard, Xpert’s sensitivity and specificity was 94.9% and 88.0%, respectively. In addition, we discovered several rare or novel mutations among the North Korean Mycobacterium tuberculosis isolates.Conclusions: RIF detection in North Korea is possible using Xpert as an alternative to pDST, as this research has shown. This research is not only imperative to North Korea, but also in locations where there is limited access to conventional pDST.

scholarly journals Emergence and Transmission of Drug-/Multidrug-resistant Mycobacterium leprae in a Former Leprosy Colony in the Brazilian Amazon

2019 ◽  
Vol 70 (10) ◽  
pp. 2054-2061 ◽  
Author(s):  
Patrícia S Rosa ◽  
Helena R S D’Espindula ◽  
Ana C L Melo ◽  
Amanda N B Fontes ◽  
Amanda J Finardi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Tandem Repeats ◽  
Bacterial Resistance ◽  
Direct Sequencing ◽  
Mycobacterium Leprae ◽  
Brazilian Amazon ◽  
Multidrug Resistant ◽  
Population Based ◽  
Variable Number

AbstractBackgroundLeprosy has been treated with multidrug therapy, which has been distributed for free across the globe and regarded as highly efficient. However, the impossibility of growing Mycobacterium leprae in axenic media has historically impaired assessments of M. leprae resistance, a parameter only recently detectable through molecular methods.MethodsA systematic, population-based search for M. leprae resistance in suspected leprosy relapse cases and contacts was performed in Prata Village, an isolated, hyperendemic, former leprosy colony located in the Brazilian Amazon. Results led to an extended active search involving the entire Prata population. Confirmed leprosy cases were investigated for bacterial resistance using a combination of in vivo testing and direct sequencing of resistance genes folP1, rpoB, and gyrA. A molecular epidemiology analysis was performed using data from 17 variable number tandem repeats (VNTR).ResultsMycobacterium leprae was obtained from biopsies of 37 leprosy cases (18 relapses and 19 new cases): 16 (43.24%) displayed drug-resistance variants. Multidrug resistance to rifampicin and dapsone was observed in 8 relapses and 4 new cases. Single resistance to rifampicin was detected in 1 new case. Resistance to dapsone was present in 2 relapses and 1 new case. Combined molecular resistance and VNTR data revealed evidence of intra-familial primary transmission of resistant M. leprae.ConclusionsA comprehensive, population-based systematic approach to investigate M. leprae resistance in a unique population revealed an alarming scenario of the emergence and transmission of resistant strains. These findings may be used for the development of new strategies for surveillance of drug resistance in other populations.

Molecular Characterization of Levofloxacin, Moxifloxacin, Bedaquiline, Linezolid, Clofazimine, and Delamanid against Multidrug-resistant Tuberculosis in Southwest of China

2021 ◽  
Author(s):  
Huiwen Zheng ◽  
Wencong He ◽  
Weiwei Jiao ◽  
Hui Xia ◽  
Lin Sun ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Southwest China ◽  
Resistance Mutation ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Genetic Characteristics ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Objectives: To explore the drug susceptibility of levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ) and delamanid (DLM) against multidrug resistant tuberculosis (MDR-TB) isolates from drug resistance survey of southwest China, and to illustrate the genetic characteristics of MDR-TB isolates with acquired drug resistance. Methods: A total of 339 strains were collected from smear-positive TB patients in the drug resistance survey of southwest China between January 2014 and December 2016. The MICs were determined for MDR-TB identified by conventional drug susceptibility testing. Genes related to drug resistance were amplified with their corresponding pairs of primers. Results: MDR was observed in 88 (26.0%; 88/339) isolates. LFX had the highest resistance rate (50.0%; 44/88), followed by MFX (38.6%; 34/88). The resistance rate to LZD, CFZ, and DLM was 4.5% (4/88), 3.4% (3/88), and 4.5% (4/88), respectively, and the lowest resistance rate was observed in BDQ (2.3%; 2/88). Of the 45 isolates resistant to LFX and MFX, the most prevalent resistance mutation was found in gyrA with the substitution of codon 94 (34/45, 75.6%). All two CFZ - BDQ cross resistant strains had a mutation in the Rv0678 gene. Two of four LZD resistant isolates carried mutations in rplC gene. Of the four isolates resistant to DLM, one isolate with the mutations in codon 318 of fbiC gene and two isolates in codon 81 of ddn gene. Conclusion: This study provided evidence for further application of new anti-TB drugs in the treatment of MDR-TB in China.

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